Snapin Facilitates the Synchronization of Synaptic Vesicle Fusion

Neuron. 2009 Feb 12;61(3):412-24. doi: 10.1016/j.neuron.2008.12.029.

Abstract

Synaptic vesicle (SV) fusion is a fine-tuned process requiring a concert of fusion machineries. Using cortical neurons from snapin-deficient mice, we reveal a role for Snapin in facilitating synchronous release. In addition to reduced frequency of miniature excitatory postsynaptic currents (mini-EPSCs) and smaller release-ready vesicle pool (RRP) size, snapin deficiency results in EPSCs with multiple peaks and increased rise and decay times, reflecting "desynchronized" SV fusion. These defects impair both synaptic precision and efficacy during sustained neurotransmission. Transient expression of Snapin not only rescues the slowed kinetics of EPSCs, but also further accelerates the rate found in wild-type neurons. Furthermore, expression of Snapin-C66A, a dimerization-defective mutant with impaired interactions with SNAP-25 and Synaptotagmin, reduces the RRP size but exhibits less effect on synchronized fusion. Our studies provide mechanistic insights into a dual role of Snapin in enhancing the efficacy of SV priming and in fine-tuning synchronous SV fusion.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / genetics*
  • Membrane Fusion / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation / genetics
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Synaptic Transmission / genetics*
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure
  • Synaptosomal-Associated Protein 25 / genetics
  • Synaptosomal-Associated Protein 25 / metabolism
  • Synaptotagmins / genetics
  • Synaptotagmins / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • Snapin protein, mouse
  • Synaptosomal-Associated Protein 25
  • Vesicular Transport Proteins
  • Synaptotagmins